1D-3D hybrid modeling—from multi-compartment models to full resolution models in space and time

Investigation of cellular and network dynamics in the brain by means of modeling & simulation has evolved into a highly interdisciplinary field, that uses sophisticated modeling & simulation approaches to understand distinct areas of brain function. Depending on the underlying complexity, these models vary in level of detail to cope with the attached computational cost. Hence for large network simulations, single neurons are typically reduced to time-dependent signal processors, dismissing spatial aspects of the cells. For single cell or small-world networks, general purpose simulators allow for space and time-dependent simulations of electrical signal processing, based on the cable equation theory. An emerging field in Computational Neuroscience encompasses a new level of detail by incorporating the 3D morphology of cells and organelles into 3D space and time-dependent simulations. Every approach has its advantages and limitations, such as computational cost, integrated and methods-spanning simulation approaches, depending on the network size could establish new ways to investigate the brain. We present a hybrid simulation approach, that makes use of reduced 1D-models using e.g. the NEURON which couples to fully resolved models for simulating cellular and sub-cellular dynamics, including the detailed 3D-morphology of neurons and organelles. To couple 1D- & 3D-simulations, we present a geometry and membrane potential mapping framework, with which graph-based morphologies, e.g. in swc-/hoc-format, are mapped to full surface and volume representations of the neuron; membrane potential data from 1D-simulations are used as boundary conditions for full 3D simulations. Thus, established models and data, based on general purpose 1D-simulators, can be directly coupled to the emerging field of fully resolved highly detailed 3D-modeling approaches. The new framework is applied to investigate electrically active neurons and their intracellular spatio-temporal Calcium Dynamics

Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Geometry Processing of Conventionally Produced Mouse Brain Slice Images

Brain mapping research in most neuroanatomical laboratories relies on conventional processing techniques, which often introduce histological artifacts such as tissue tears and tissue loss. In this paper we present techniques and algorithms for automatic registration and 3D reconstruction of conventionally produced mouse brain slices in a standardized atlas space. This is achieved first by constructing a virtual 3D mouse brain model from annotated slices of Allen Reference Atlas (ARA). Virtual re-slicing of the reconstructed model generates ARA-based slice images corresponding to the microscopic images of histological brain sections. These image pairs are aligned using a geometric approach through contour images. Histological artifacts in the microscopic images are detected and removed using Constrained Delaunay Triangulation before performing global alignment. Finally, non-linear registration is performed by solving Laplace's equation with Dirichlet boundary conditions. Our methods provide significant improvements over previously reported registration techniques for the tested slices in 3D space, especially on slices with significant histological artifacts. Further, as an application we count the number of neurons in various anatomical regions using a dataset of 51 microscopic slices from a single mouse brain. This work represents a significant contribution to this subfield of neuroscience as it provides tools to neuroanatomist for analyzing and processing histological data.Comment: 14 pages, 11 figure

Rendering techniques for multimodal data

Many different direct volume rendering methods have been developed to visualize 3D scalar fields on uniform rectilinear grids. However, little work has been done on rendering simultaneously various properties of the same 3D region measured with different registration devices or at different instants of time. The demand for this type of visualization is rapidly increasing in scientific applications such as medicine in which the visual integration of multiple modalities allows a better comprehension of the anatomy and a perception of its relationships with activity. This paper presents different strategies of Direct Multimodal Volume Rendering (DMVR). It is restricted to voxel models with a known 3D rigid alignment transformation. The paper evaluates at which steps of the render-ing pipeline must the data fusion be realized in order to accomplish the desired visual integration and to provide fast re-renders when some fusion parameters are modified. In addition, it analyzes how existing monomodal visualization al-gorithms can be extended to multiple datasets and it compares their efficiency and their computational cost.Postprint (published version

Geometric Convolutional Neural Network for Analyzing Surface-Based Neuroimaging Data

The conventional CNN, widely used for two-dimensional images, however, is not directly applicable to non-regular geometric surface, such as a cortical thickness. We propose Geometric CNN (gCNN) that deals with data representation over a spherical surface and renders pattern recognition in a multi-shell mesh structure. The classification accuracy for sex was significantly higher than that of SVM and image based CNN. It only uses MRI thickness data to classify gender but this method can expand to classify disease from other MRI or fMRI dataComment: 29 page

Cortical depth dependent functional responses in humans at 7T: improved specificity with 3D GRASE

Ultra high fields (7T and above) allow functional imaging with high contrast-to-noise ratios and improved spatial resolution. This, along with improved hardware and imaging techniques, allow investigating columnar and laminar functional responses. Using gradient-echo (GE) (T2* weighted) based sequences, layer specific responses have been recorded from human (and animal) primary visual areas. However, their increased sensitivity to large surface veins potentially clouds detecting and interpreting layer specific responses. Conversely, spin-echo (SE) (T2 weighted) sequences are less sensitive to large veins and have been used to map cortical columns in humans. T2 weighted 3D GRASE with inner volume selection provides high isotropic resolution over extended volumes, overcoming some of the many technical limitations of conventional 2D SE-EPI, whereby making layer specific investigations feasible. Further, the demonstration of columnar level specificity with 3D GRASE, despite contributions from both stimulated echoes and conventional T2 contrast, has made it an attractive alternative over 2D SE-EPI. Here, we assess the spatial specificity of cortical depth dependent 3D GRASE functional responses in human V1 and hMT by comparing it to GE responses. In doing so we demonstrate that 3D GRASE is less sensitive to contributions from large veins in superficial layers, while showing increased specificity (functional tuning) throughout the cortex compared to GE

Registration of brain tumor images using hyper-elastic regularization

In this paper, we present a method to estimate a deformation field between two instances of a brain volume having tumor. The novelties include the assessment of the disease progress by observing the healthy tissue deformation and usage of the Neo-Hookean strain energy density model as a regularizer in deformable registration framework. Implementations on synthetic and patient data provide promising results, which might have relevant use in clinical problems

3D time series analysis of cell shape using Laplacian approaches

Background: Fundamental cellular processes such as cell movement, division or food uptake critically depend on cells being able to change shape. Fast acquisition of three-dimensional image time series has now become possible, but we lack efficient tools for analysing shape deformations in order to understand the real three-dimensional nature of shape changes. Results: We present a framework for 3D+time cell shape analysis. The main contribution is three-fold: First, we develop a fast, automatic random walker method for cell segmentation. Second, a novel topology fixing method is proposed to fix segmented binary volumes without spherical topology. Third, we show that algorithms used for each individual step of the analysis pipeline (cell segmentation, topology fixing, spherical parameterization, and shape representation) are closely related to the Laplacian operator. The framework is applied to the shape analysis of neutrophil cells. Conclusions: The method we propose for cell segmentation is faster than the traditional random walker method or the level set method, and performs better on 3D time-series of neutrophil cells, which are comparatively noisy as stacks have to be acquired fast enough to account for cell motion. Our method for topology fixing outperforms the tools provided by SPHARM-MAT and SPHARM-PDM in terms of their successful fixing rates. The different tasks in the presented pipeline for 3D+time shape analysis of cells can be solved using Laplacian approaches, opening the possibility of eventually combining individual steps in order to speed up computations